Effects of Genetic Variants of Nuclear Receptor Y on the Risk of Type 2 Diabetes Mellitus
Effects of Genetic Variants of Nuclear Receptor Y on the Risk of Type 2 Diabetes Mellitus
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核受体 Y 的遗传变异对 2 型糖尿病风险的影响
DOI：
10.1155/2019/4902301
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发表时间：
2019-05
影响因子：
4.3
通讯作者：
Su Zhiguang
中科院分区：
文献类型：
--
作者：
Wang Ying;Yang Shanshan;Guan Qiuyue;Chen Jinglu;Zhang Xueping;Zhang Yuwei;Yuan Yiming;Su Zhiguang
核因子-Y (NF-Y) 由三个进化保守亚基组成，包括 NF-YA、NF-YB 和 NF-YC；它是与 2 型糖尿病 (T2DM) 发生相关的脂质和葡萄糖代谢以及脂肪因子生物合成的关键转录调节因子，而 NF-Y 基因的遗传变异对 T2DM 风险的影响仍有待研究。在本研究中，我们采用 SNaPshot 方法在 427 名 T2DM 患者和 408 名健康个体中筛选了 5 个单核苷酸多态性 (SNP)。随后，我们分析了在不同遗传模型下由这些 SNP 构建的基因型和单倍型与 T2DM 之间的关系。此外，我们研究了等位基因对数量代谢性状的影响。在 5 个 tagSNP 中，我们发现 3 个 SNP（rs2268188、rs6918969 和 rs28869187）在 T2DM 患者和健康个体之间的等位基因或基因型频率上表现出名义上的显着差异。 rs2268188、rs6918969和rs28869187的次要等位基因G、C和C分别在显性遗传模型下赋予较高的T2DM风险，并且这些风险等位基因的携带者（次要等位基因的纯合子或杂合子）具有统计学上更高的空腹血糖、胆固醇和甘油三酯水平。单倍型分析显示，SNP rs2268188、rs6918969、rs28869187 和 rs35105472 形成单倍型块，单倍型 TTAC 对 T2DM 具有保护作用（OR = 0.76，95% CI = 0.33-0.82，P = 0.004），而单倍型GCCG 与 T2DM 易感性升高相关（OR = 2.33，95% CI = 1.43-3.57，P = 0.001）。据我们所知，这项研究是首次观察表明 NF-YA 的遗传变异可能影响中国汉族个体 T2DM 的发生。
Nuclear factor-Y (NF-Y) consists of three evolutionary conserved subunits including NF-YA, NF-YB, and NF-YC; it is a critical transcriptional regulator of lipid and glucose metabolism and adipokine biosynthesis that are associated with type 2 diabetes mellitus (T2DM) occurrence, while the impacts of genetic variants in the NF-Y gene on the risk of T2DM remain to be investigated. In the present study, we screened five single-nucleotide polymorphisms (SNPs) with the SNaPshot method in 427 patients with T2DM and 408 healthy individuals. Subsequently, we analyzed the relationships between genotypes and haplotypes constructed from these SNPs with T2DM under diverse genetic models. Furthermore, we investigated the allele effects on the quantitative metabolic traits. Of the five tagSNPs, we found that three SNPs (rs2268188, rs6918969, and rs28869187) exhibited nominal significant differences in allelic or genotypic frequency between patients with T2DM and healthy individuals. The minor alleles G, C, and C at rs2268188, rs6918969, and rs28869187, respectively, conferred a higher T2DM risk under a dominant genetic model, and the carriers of these risk alleles (either homozygotes of the minor allele or heterozygotes) had statistically higher levels of fasting plasma glucose, cholesterol, and triglycerides. Haplotype analysis showed that SNPs rs2268188, rs6918969, rs28869187, and rs35105472 formed a haplotype block, and haplotype TTAC was protective against T2DM (OR = 0.76, 95% CI = 0.33-0.82, P = 0.004), while haplotype GCCG was associated with an elevated susceptibility to T2DM (OR = 2.33, 95% CI = 1.43-3.57, P = 0.001). This study is the first ever observation to our knowledge that indicates the genetic variants of NF-YA might influence a Chinese Han individual's occurrence of T2DM.
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影响因子：
5.1
作者：
Guariguata, L.;Whiting, D. R.;Shaw, J. E.
通讯作者：
Shaw, J. E.
影响因子：
8.2
作者：
Gan W;Walters RG;Holmes MV;Bragg F;Millwood IY;Banasik K;Chen Y;Du H;Iona A;Mahajan A;Yang L;Bian Z;Guo Y;Clarke RJ;Li L;McCarthy MI;Chen Z;China Kadoorie Biobank Collaborative Group
通讯作者：
China Kadoorie Biobank Collaborative Group
影响因子：
3.1
作者：
M. Téran-García;C. Rufo;Manabu T. Nakamura;T. Osborne;S. Clarke
通讯作者：
M. Téran-García;C. Rufo;Manabu T. Nakamura;T. Osborne;S. Clarke
肥胖诱导的内质网应激抑制核因子-Y 表达
影响因子：
4.3
作者：
Liu, Yulan;Zhang, Yuwei;Su, Zhiguang
通讯作者：
Su, Zhiguang
DOI：
10.1073/pnas.040574197
发表时间：
2000-04
影响因子：
11.1
作者：
S. Xiong;S. Chirala;S. Wakil
通讯作者：
S. Xiong;S. Chirala;S. Wakil